The long-term objective of this application is to help eliminate the suffering and death of children with brain cancer. Brain cancers are the most common solid tumors in children. Survival remains poor for patients with metastases or recurrence;current therapy commonly causes severe neurocognitive deficits. The leading institutions include the University of Washington (UW), the Fred Hutchinson Cancer Research Center (FHCRC), Children's Hospital &Regional Medical Center (CHRMC), and Philips Medical Systems (PMS). Our multidisciplinary approach includes expertise in Materials Science (Miqin Zhang (UW), Lead Investigator for iron oxide nanoparticle synthesis for tumor targeting, imaging, and treatment);molecular tumor biology (James Olson (FHCRC, UW, CHRMC), Lead Investigator for in vitro and in vivo models of pediatric brain cancer);MR imaging physics (Donghoon Lee (UW) and Stefan Fischer (PMS), Lead Investigators for optimization of small animal coil design, pulse sequences, and signal quantification);and clinical and small animal diagnostic imaging interpretation (Raymond Sze (UW, CHRMC), Principal Investigator). The Specific Aims (and Cancer Focus Areas) are: Aim 1 (Reporters of therapeutic efficacy): develop a tumor-targeting dual MR and optical nanoparticulate contrast agent that will enable presurgical planning and intraoperative delineation of tumor margins;Aim 2 (Multifunctional therapeutics): develop a tumor-targeted dual MR and optical nanoparticulate imaging agent carrying a chemotherapeutic payload. Following synthesis of the multifunctional nanoparticles, targeting specificity, contrast dose, timing of scanning, image contrast, and therapeutic efficacy will be optimized progressively in in vitro then in vivo flank xenograft and spontaneous intracranial mouse models of pediatric brain cancer. Public health relevance: the tumor targeting nanoparticle agents proposed may enable dramatically improved diagnosis and treatment for children with brain cancer while concurrently reducing the frequently severe complications resulting from current treatment-related toxicities.